Vit Prochazka1, Marie Lukasova1, Eva Kriegova2, Alice Sykorova3, Heidi Mocikova4, Tomas Papajik1, David Belada3, Jana Markova4, Katerina Klaskova4, Veronika Hanackova1, Gabriela Gabcova2, Zuzana Mikulková2, Pavla Stepankova3, on behalf of the Czech Hodgkin Lymphoma Study Group
1Department of Haemato-Oncology, Faculty of Medicine and Dentistry, Palacky, University and University Hospital Olomouc, Czech Republic,2Olgen research center, Department of Immunology, Faculty of Medicine and Dentistry, Palacky University and University Hospital Olomouc, Czech Republic,3Fourth Department of Internal Medicine - Haematology, Charles University, Hospital and Faculty of Medicine, Hradec Kralove, Czech Republic,4Department of Internal Medicine and Haematology, Faculty Hospital Kralovske Vinohrady and Third Faculty of Medicine, Charles University in Prague, Czech Republic
Background: In patients with Hodgkin lymphoma (HL), serum concentrations of thymus and activation-regulated chemokine (TARC) and other cytokines have been proved to have prognostic significance in the patients treated with ABVD. The potential utility has not been tested in the landmark population treated according to the GHSG policy. With new, abbreviated interim PET-tailored chemotherapy schemes (2+2) and reduced radiotherapy protocols, there is a clinical need for additional predictors of the therapy failure.
Aim: To analyze cytokine profile in a prospective, unselected real-life cohort of the HL pts and correlate it with the conventional prognostic factors and the treatment outcome.
Methods: We have analyzed a set of four biomarkers: soluble CD30 (sCD30), soluble CD163 (sCD163), TARC, and interleukin 6 (IL6), which were measured in serum using ELISA assays (R and D, Novus Biotechne Brand) according to the manufacturer's recommendations.
Results: In total, we have analyzed 168 samples of 107 patients and 21 age-sex matched healthy controls (HC). Eighty patients were sampled at the time of initial diagnosis (DG), Nine after a 2nd or 3rd cycle of therapy, six after treatment and twelve with relapsed/refractory disease (RR). When compared HC and DG pts, all 4 cytokines were highly elevated in DG: 15.5 vs 87.4 ng/mL, p < 0.001; 338 vs 7711 pg/mL, p < 0.001; 426 vs 800 ng/mL, p < 0.001 and 0.1 vs 8.4 pg/mL for median values of sCD30, TARC, sCD163 and IL-6, respectively. In DG pts, all four cytokines correlated with GHSG stage, but only sCD30 and TARC were significantly different when compared intermediate to limited (p = 0.05, p < 0.001) stage. sCD30 was significantly higher in advanced compared to the intermediate stage (p = 0.03). Subanalysis of pts in the advanced stage shown no correlation of low vs. high IPS score and cytokines, except for IL-6 (5.15 vs. 34.4 pg/mL, p = 0.001). Pretreatment levels of sCD163 (p = 0.002) and IL-6 (p = 0.06) were correlated with achieving CR.
Conclusion: Cytokines, reflecting tumor load (sCD30, TARC), lymphoma-associated macrophages activity (sCD163) and inflammation (IL-6) have a relationship to the characteristics of the disease, correlate with remission status and probably may potential to improve risk stratification in particular cases. Longer follow-up is needed to establish their prognostic role in the population-based setting.
Acknowledgment: LF UP_2018_004, MH CZ–DRO (FNOL, 00098892)